PKDef bij Maine Coon.

Omdat bij de dna-test van PPotch 2 allelen van het gen PKdef zijn gevonden hebben we ons verdiept in wat PKDef voor de Maine Coon inhoud. Bekend is dat als een kat maar 1 allel heeft, deze niet ziek kan worden omdat het een recessief gen is.

Onderstaande is een stukje tekst over PKDef van de site van CombiBreed van Dr. van Haeringen Laboratorium b.v.

Pyruvaat Kinase (PK) is een enzym dat essentieel is voor de energieproductie in rode bloedcellen. Bij lijders is dit enzym afwezig, waardoor rode bloedcellen versneld afgebroken worden. De afwijking kenmerkt zich door bloedarmoede. Bij diverse rassen is een verschillende mate van de symptomen beschreven.

Zoals hierboven beschreven staat zijn er verschillende mate van symptomen bekend bij diverse rassen, dus was onze vraag: “ welke symptomen komen nu voor bij het ras Maine Coon? “

In onze speurtocht op het grote web kwamen we in contact met een Deense fokker die onderzoek doet naar PKDef bij Maine Coons. Bij haar zijn er nog geen gevallen bekend van katten die ziekteverschijnselen laten zien als ze 2 allelen hebben van PKDef, in de volksmond worden deze katten “lijders” genoemd. Er zijn bij haar wel 2 gevallen bekend van lijders, een kater van 5 jaar en een poes van 6 jaar die al 2 nestjes heeft gehad en deze vertonen geen ziekteverschijnselen.

De fokster van PPotch heeft ook onderzoek gedaan en heeft mailwisselingen met vragen en antwoorden gehad met 2 professoren in Amerika, Leslie Lyons en Urs Giger. Beiden hebben in hun onderzoeken geen katten van het ras Maine Coon gezien die lijder waren en ziekteverschijnselen vertoonden.

Tijdens onze zoektocht naar informatie over PKDef kwamen we er ook achter dat er bij de fokkers van dit mooie ras veel verschillende meningen zijn over eventuele ziekteverschijnselen bij de Maine Coon en het fokken met een “lijder”.

Wij denken dat bij lijders van PKDef van het ras Maine Coon geen ziekteverschijnselen ontstaan, en daarom hebben we besloten om PPotch niet te laten steriliseren, PPotch heeft ook een genetische diversiteit van 39% wat erg hoog is voor het ras, en het zou zonde zijn om dit verloren te laten gaan.

Hoe gaan we nu verder:

Omdat bekend is dat een drager van PKDef ( dus maar 1 allel ) zeker geen ziekteverschijnselen kan vertonen willen we een nestje van PPotch met een kater die negatief getest is voor PKDef. Zodoende zullen er kittens geboren worden die

drager zijn, maar niet ziek kunnen worden. De bedoeling is dan om een poes uit dit nest aan te houden zodat de lijn met hoge genen diversiteit door kan gaan.

PPotch zal deelnemen aan het onderzoek wat in Denemarken loopt. Haar bloed zal regelmatig onderzocht worden op afwijkende waardes door het Universitair Veterinair Diagnostisch Laboratorium in Utrecht. Dit is gedaan op 16-09-2021 op 18-01-2022 dit was voor de zwangerschap en 10-11-2022 dit was na de geboorte  en er waren geen afwijkende waardes te zien. Onderaan deze pagina kunt u doorklikken naar de uitslagen.

Hopelijk kunnen we op deze manier aantonen dat PKDef geen ziekteverschijnselen geeft bij het ras Maine Coon.

Hieronder zijn de vragen en antwoorden van Prof. Urs Giger:

Marjan’s specific question’s stated October 30, 2021:

Short answers:

As little to no PK Deficiency affected Maine Coon cats have been found ever since the allele was found in the MC (to my knowledge that is), why do we need to test MC's for it?

It is easy to screen as part of a Maine Coon breed panel, but likely not need to specifically test unless you know of PK-deficient affecteds and carriers or a Maine Coon cat is anemic.

What criteria do laboratories have/or need, to recommend breeders/owners to use the test?

Laboratories mostly follow published information and adopt breed club recommendations unless it is a research laboratory with firsthand data.

Could the deficiency become a problem for MC's in the future? If so, what time frame could be expected?

I have never seen a Maine Coon with PK deficiency. There is no reason to believe this could become a major problem in the Maine Coon breed as long as those who have known PK-affecteds and carriers use them without testing mates.

Long answers:

Bearing all this in mind, what would your breeding-recommendations for breeders be?

As little to no PK Deficiency affected Maine Coon cats have been found ever since the allele was found in the MC (to my knowledge that is), why do we need to test MC's for it?

An increasing number of hereditary disorders have been recognized in domestic cats with some causing only mild signs while others are or can be devastating. Many of them have been studied and for about three dozen hereditary disease traits there is a DNA test. They are either testing for a specific pathogenic mutation in a gene or are DNA markers closely associated with the disease.

Most hereditary diseases and gene mutations are breed specific but some are seen in several breeds due to the early ancestral occurrence. The Maine Coon breed has been the focus of many studies and indeed a variety of hereditary diseases and gene mutations have been described in the breed. It is crucial for Maine Coon breeders, but also for owners of and veterinary clinicians attending to Maine Coon cats to know the breed specific deleterious traits. Ideally the potential occurrence of these disorders would be considered prior to breeding and during initial wellness exams and not only when a cat has fallen ill.

My laboratory at PennGen discovered pyruvate kinase (PK) deficiency in 1991 and found the PK gene mutation in 1998. Originally we found PK deficiency in Abyssinian and Somali cats but then also in regular non-purpose-bred cats and other breeds. It turns out to be a common ancestral gene mutation, and is the very same in all the breeds where PK deficiency has been found. And due to interbreeding of breeds it may be seen rarely in other breeds.

The enzyme PK is important in generating energy (ATP) in the last step of glucose breakdown.

PK deficiency in cats is an autosomal-recessive trait and can cause an intermitted to chronic anemia occasionally requiring transfusions for very severely anemic cats (hemolytic crises). It can also rarely cause gall bladder stones with icterus. Note, clinical signs of anemia are highly variable and crises may be triggered by infections and other environmental factors. Many cats can live very well with PK deficiency and reach normal life expectancy. Nevertheless, it is important to have a specific diagnosis to manage the PK deficient cat appropriately and not to subject it to unnecessary and costly diagnostics and treatments. Moreover, PK deficiency should not be confused with PKD which stands for polycystic kidney disease which may cause renal failure.

I have been involved in the study of a variety of genetic traits in Maine Coon cats including musculoskeletal abnormalities, such as hip dysplasia as well as spinal muscular atrophy, and blood related disorders such A-B blood incompatibilities as well as recently coagulation

factor XI deficiency (see below).

I have never seen or heard of any PK deficient Maine Coon cats. Thus I cannot comment on the severity of the disease in the breed. In my assessment, PK deficiency is not a major health issue in Maine Coon cats and does not need to specifically tested for. However, as breed-specific panel DNA tests become more standard (e.g. Laboklin), it may well be worthy to include a commonly occurring mutation such as PK deficiency which adds little costs. Because PK deficiency is rare, related cats should be screened if any Maine Coon cat is found to carry the PK mutant allele in order to limit the further spread in the breed.

What criteria do laboratories have/or need, to recommend breeders/owners to use the test?

Veterinary diagnostic laboratories use generally published information and may include their own experience which may be unique to a specific regions. There are efforts by veterinarians and breed clubs to make more informed recommendations. Moreover, there are also regulations by specific governments requiring certain tests prior to breeding or selling.

Generally, DNA tests for diseases documented in a breed are of great benefit as they allow a precise diagnosis of affecteds and informed breeding – PK carriers can be safely bred to clear for recessive traits and as long as all offspring intended for breeding are tested the production of any affected cats can be avoided.

Could the PK deficiency become a problem for MC's in the future? If so, what time frame could be expected?

Considering the fact that health conscious breeders will screen their cats prior to breeding for known traits, panel tests will become the norm, and veterinary clinicians are informed about PK deficiency, because it is one of the common hereditary disorders in several feline breeds, I cannot imagine that PK deficiency is going to be ever a problem in the Maine Coon breed.

I like to add an example of a very recently discovered hereditary blood disorder in the Maine Coon breed – coagulation factor XI (FXI) deficiency. A little more than one year ago, I was contacted by a couple of breeders about a mild-moderate bleeding problem which is caused by a clotting factor missing in blood (plasma) of affected Maine Coon cats. In collaboration with others we studied this disorder, identified a mutation in the F11 gene. And to our surprise this autosomal recessive trait exists commonly in Maine Coon cats in USA and Europe. Laboklin which did most of the investigations is now offering this DNA test and a peer-reviewed

publication is being prepared. Certainly any bleeding Maine Coon cat (or if the cat has an aPTT prolongation) should be screened to reach a precise diagnosis. This is a new and mild bleeding tendency and the F11 mutation seems common in the breed, specific breeding recommendations still need to be adjusted.

Bearing all this in mind, what would your breeding-recommendations for breeders be?

I believe my long answers with ample background information contain my recommendations. It would be best if the breed health committee would come up with a list of the hereditary diseases seen in the breed and classify them according to severity, treatability, availability of a specific diagnostic test, and commonness. Some of the information may need to be gathered by breeders by a survey and sharing information. I suggest to use breed-specific DNA test panels from reliable DNA testing laboratories. Any Maine Coon cat affected should be further assessed and managed by a veterinarian and excluded from breeding. Carriers of autosomal recessive traits can safely bred to tested clear cats – and their offspring should be tested before breeding.

With kind regards

Urs Giger

Urs Giger, Prof. Dr. med. vet., MS, FVH

Dipl. ACVIM-SA & ECVIM-CA (Internal Medicine)

Dipl. ECVCP (Clinical Pathology)

Emeritus Charlotte Newton Sheppard Endowed Professor of Medicine Chair

School of Veterinary Medicine, University of Pennsylvania

Emeritus Professor of Hematology

School of Medicine, University of Pennsylvania

Professor of Small Animal Internal Medicine

Vetsuisse, University of Zürich